Transgenic mice with pigmented intraocular tumors

Tissue of origin and treatment

Nasreen A. Syed, Jolene J. Windle, Soesiawati R. Darjatmoko, Janice M. Lokken, Richard A. Steeves, Rick Chappell, Ingolf H.L. Wallow, Barbara A. Koop, Gina Mangold, Kimberly A. Howes, Daniel Albert

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

PURPOSE. To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS. Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS. Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS. Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

Original languageEnglish (US)
Pages (from-to)2800-2805
Number of pages6
JournalInvestigative Ophthalmology and Visual Science
Volume39
Issue number13
StatePublished - Dec 1 1998
Externally publishedYes

Fingerprint

Transgenic Mice
Neoplasms
Therapeutics
Melanoma
Dacarbazine
Electron Microscopy
Polyomavirus Transforming Antigens
Melanosomes
Light
Fas Ligand Protein
Retinal Pigments
Survival
Monophenol Monooxygenase
Penetrance
Retinal Pigment Epithelium
Microvilli
Basement Membrane
Endoplasmic Reticulum
Microscopy
Histology

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Syed, N. A., Windle, J. J., Darjatmoko, S. R., Lokken, J. M., Steeves, R. A., Chappell, R., ... Albert, D. (1998). Transgenic mice with pigmented intraocular tumors: Tissue of origin and treatment. Investigative Ophthalmology and Visual Science, 39(13), 2800-2805.

Transgenic mice with pigmented intraocular tumors : Tissue of origin and treatment. / Syed, Nasreen A.; Windle, Jolene J.; Darjatmoko, Soesiawati R.; Lokken, Janice M.; Steeves, Richard A.; Chappell, Rick; Wallow, Ingolf H.L.; Koop, Barbara A.; Mangold, Gina; Howes, Kimberly A.; Albert, Daniel.

In: Investigative Ophthalmology and Visual Science, Vol. 39, No. 13, 01.12.1998, p. 2800-2805.

Research output: Contribution to journalArticle

Syed, NA, Windle, JJ, Darjatmoko, SR, Lokken, JM, Steeves, RA, Chappell, R, Wallow, IHL, Koop, BA, Mangold, G, Howes, KA & Albert, D 1998, 'Transgenic mice with pigmented intraocular tumors: Tissue of origin and treatment', Investigative Ophthalmology and Visual Science, vol. 39, no. 13, pp. 2800-2805.
Syed NA, Windle JJ, Darjatmoko SR, Lokken JM, Steeves RA, Chappell R et al. Transgenic mice with pigmented intraocular tumors: Tissue of origin and treatment. Investigative Ophthalmology and Visual Science. 1998 Dec 1;39(13):2800-2805.
Syed, Nasreen A. ; Windle, Jolene J. ; Darjatmoko, Soesiawati R. ; Lokken, Janice M. ; Steeves, Richard A. ; Chappell, Rick ; Wallow, Ingolf H.L. ; Koop, Barbara A. ; Mangold, Gina ; Howes, Kimberly A. ; Albert, Daniel. / Transgenic mice with pigmented intraocular tumors : Tissue of origin and treatment. In: Investigative Ophthalmology and Visual Science. 1998 ; Vol. 39, No. 13. pp. 2800-2805.
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abstract = "PURPOSE. To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS. Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS. Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS. Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.",
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AU - Lokken, Janice M.

AU - Steeves, Richard A.

AU - Chappell, Rick

AU - Wallow, Ingolf H.L.

AU - Koop, Barbara A.

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AU - Howes, Kimberly A.

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N2 - PURPOSE. To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS. Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS. Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS. Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

AB - PURPOSE. To describe the cell of origin, tumor progression, light and electron microscopic appearance, immunohistochemical properties, and response to frequently used anticancer therapies in two transgenic models of intraocular melanoma. METHODS. Two lines of transgenic mice that develop pigmented intraocular tumors were produced with the SV40 T and t antigens under the control of the mouse tyrosinase gene. Tumors were sequentially studied and characterized by light microscopy, electron microscopy, and immunohistochemistry stains. Tumor response to two cycles of dacarbazine was assessed on the basis of tumor size in one group of animals. Response to external beam irradiation was measured by survival time in other animals. RESULTS. Two lines of transgenic mice developed bilateral intraocular tumors with complete penetrance and without primary cutaneous melanomas. Tumors developed first in the retinal pigment epithelial layer, with subsequent retinal and choroidal invasion, extraocular extension, and metastasis. Tumors stained positive for S-100, HMB-45, and Fas-ligand. Electron microscopy revealed polarization of tumor cells with basement membrane formation, microvilli, immature melanosomes, and abundant endoplasmic reticulum. Dacarbazine significantly reduced tumor size in these mice, and a trend toward dose-dependent decrease in survival was found with external beam irradiation. CONCLUSIONS. Tumors developed from the retinal pigment epithelium. Their histology and growth, however, closely resembled that of human choroidal melanoma. This model may be a useful tool for future studies of endogenous primary pigmented tumors limited to the eye. Response to standard therapies suggests it can serve as a model with which to evaluate therapeutic modalities.

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